Our goal is to evaluate the clinical activity of recombinant immunotoxins in patients. HA22 is licensed to MedImmune who is sponsoring trials in B cell malignancies. A multi center phase 1 trial of HA22 (CAT-8015, moxetumomab pasudotox) in drug resistant hairy cell leukemia is completed and is now being expanded at the MTD. There have been no dose limiting toxicities and over 50% of patients have achieved a complete remission. A multi center phase 1 trial of HA22 in refectory ALL has opened and 15 patients treated. Clinical activity with 4 complete remissions has been observed. This is a collaboration with Dr. Alan Wayne of the Pediatric Oncology Branch. Trials with LMB2 in CTL and ATL are ongoing. Dr. Hassan has treated 16 patients with mesothelioma with SS1P plus chemotherapy. An MTD has been established and at the MTD 6/9 patients have had PRs. We are now at the MTD and will treat 3more patients this dose level. Based on the high number of CRs at the MTD a randomized phase 2 trial is being planned. Another SS1P trial was just opened in which patients will receive pentostatin plus cyclophosphamide with SS1P to try and prevent neutralizing antibody formation allowing more doses to be given.